Prevention of T2DM: health economics

There is a substantial financial burden of type 2 diabetes mellitus (T2DM) not only regionally but globally, that is forecast to keep growing due to increasing prevalence of T2DM and the increasing costs of medical care. Health economic studies are designed to maintain the sustainability of healthcare system, by identifying interventions that are either cost saving or good value for money (i.e. cost-effective). Many diabetes prevention interventions have not only demonstrated efficacy in clinical trials, but have also been identified as being cost-effective or even cost saving.

Financial burden of type 2 diabetes

In the U.S., it was estimated the total cost of diagnosed T2DM in 2012 was USD 245 billion, including USD176 billion (72%) for direct medical cost and USD69 billion (28%) for indirect costs due to the productivity loss. The total costs comprised around 11% of total healthcare expenditures in adults aged between 20 and 79 years. Surprisingly, the total costs of T2DM in 2012 increased by 41% compared with the estimation in 2007 [1]. In Europe, total direct costs of T2DM varies between countries: €12.9 billion for France, €43.2 billion for Germany, €2.34 billion for Italy and €4.54 billion for the U.K. in 2010 [2]. A modelling study in Germany estimated the number of people with diabetes will grow from 5 million in 2010 to 7.9 million in 2037, and the annual cost of diabetes will increase from €11.8 billion in 2010 to €21.1 billion in 2040 [3]. Globally, the health expenditure on diabetes was expected to account for at least USD 376 billion in 2010 and will increased to USD 490 billion in 2030 [4].

The main reasons for the growth of these costs are two-fold: the increase of prevalence of T2DM and the increasing costs of medical care. The number of people with diagnosed and undiagnosed diabetes was estimated to increase from 23.7 million to 44.1 million between 2009 and 2034 [5]in the US. Among the direct medical costs, 43% of which were attributed to hospital inpatients care and the next biggest proportion (18%) was attributed to prescription medications to treat complications of diabetes. The inpatient hospital prices, on the other hand, increased roughly 6.5% between 2008 and 2010 [6].

Specifically, costs for T2DM patients with complications are even higher: with a 1.3-fold increase of annual costs in T2DM patients without complication versus the whole population. Patients with microvascular or macrovascular complications have 2.4- and 2.5-fold increases respectively. For those both have microvascular and macrovascular complications, there is a 4.1-fold increase in annual costs [7].

Apart from the direct medical costs of diabetes, costs of productivity loss (indirect costs) also contribute to the huge societal economic burden. Workdays absent, reduced performance at work, reduced productivity days for those not in labor force, reduced labor force participation due to disability and premature mortality all contribute to productivity losses. Productivity loss is likely to occur in each age group across the whole population, but not surprisingly, it affects the mid-age group (25-54 years) most.

Health economics introduction

There is great concern regarding the sustainability of global health care systems in the face of the current and future high economic burden of T2DM. Health economics and more specifically, cost effectiveness studies are used to identify new interventions that are good value for money. Typically, new interventions should be more effective than the current most commonly used approach, but on the other hand are often more expensive. When considering costs, it is important to look at the global costs of an intervention, including not only the acquisition costs of the intervention, but other additional costs like monitoring, education, side effects, as well as cost-offsets like reduced costs of complications. Cost effectiveness studies are designed to answer the question whether the additional clinical benefits seen with an intervention justify the additional costs of the intervention. A typical cost effectiveness analysis includes at least two comparators, with the incremental costs divided by the incremental effectiveness revealing the incremental cost-effectiveness ratio (ICER). Specifically, cost effectiveness analysis using quality adjusted life years (QALYs) as outcome measurement is known as cost utility analysis, and well-known nationally and internationally-recognized thresholds exist for societies’ willingness to pay (WTP) for an additional quality adjusted life-year gained by using a new intervention.

A more effective but less expensive intervention is regarded as “dominant” in the health economics sense, and would normally be immediately reimbursed by a third-party payer/decision maker (Dominant quadrant in Figure 1). Unfortunately, this situation is relatively uncommon. Less effective and more expensive interventions would typically be rejected primarily on clinical grounds (Area of Rejection in Figure 1). The majority of new interventions fall into the Figure 1. Cost effectiveness plane
Figure 1. Cost effectiveness plane
category of having improved effectiveness but increased total costs (Top right quadrant in Figure 1). Pragmatically we cannot afford all more effective interventions irrespective to their costs, alternatively a WTP threshold is adopted with interventions with ICERs greater that the WTP threshold usually being rejected. The WTP threshold varies in different countries, for example £30,000/QALY gained in the UK [8], $50,000 USD/QALY gained in the US [9]and 3 times the Gross Domestic Product (GDP) per capita/QALY gained from the World Health Organization (WHO) recommendation for developing countries [10]. Visually, the green areas in Figure 1 (area under the WTP threshold in the top right quadrant plus dominant quadrant) represent the interventions that represent good value for money.

Health economics of diabetes prevention

The objective of economic evaluations of diabetes preventions is to compare two or more strategies in terms of which strategy offers the best balance of clinical improvements versus additional costs. The economic evaluation is either performed in within-trial manner (that is evaluations using patient-level data directly from the clinical trials) or using decision analytic modelling. A number of clinical trials have demonstrated T2DM is preventable, such as the Da Qing impaired glucose tolerance (IGT) and Diabetes Study [11], the Finnish Diabetes Prevention Study (FDPS) [12] and the Diabetes Prevention Program (DPP) [13]. Using the data from these trials, short-term within-trial cost-effectiveness of intervention has been determined versus comparators [14][15]. On the other hand, decision analytic modelling studies have projected the clinical trial results by extrapolating within-trial data to a longer time horizon than the trial period.

Lifestyle modification

Lifestyle intervention was proved an effective approach for diabetes prevention, however, it was shown there was a wide variation in effectiveness in clinical studies [16]. Cost-effectiveness of lifestyle intervention for the primary prevention of T2DM in overweight/obese subjects with abnormal glucose tolerance was analyzed alongside the DPP using a short term, within-trial 3-year time horizon [15]. The study was performed using both societal and heath care system perspective. The intervention cost more than standard advice lifestyle but was cost-effective from the health system perspective: the ICER was approximately $34,543 (using 2000 U.S. dollars) per QALY gained. However, it was not cost-effective using a societal perspective with an ICER of $54,613 per QALY gained. In 2013, an updated cost effectiveness analysis was performed using 10-year open label long-term follow-up data from DPP trial and the Outcomes Study (DPPOS) [14]. Lifestyle intervention was cost saving from a health system perspective or cost-effective comparing with standard care: the ICER was $3,235 per QALY gained on societal perspective.

Trial data were also used in long-term modelled cost-effectiveness analyses on lifestyle change intervention to prevent T2DM by other research groups, and the results suggested lifestyle change intervention was cost effective or even cost saving in a variety of contexts. Using DPP data, intensive lifestyle modification was projected to be cost-saving in overweight/obese patients with IGT in Australia, France, Germany, Switzerland and was cost-effective in the United Kingdom, whereas the cost per LYG was $8,300 [17]. Similarly, lifestyle intervention was found cost-saving from the Swedish healthcare payer’ perspective, this study was also based on decision analytic modeling with data from FDPS trial [18]. Palmer et al performed a long-term modelling study using data from DPP and the DPPOS, and also demonstrated intensive lifestyle change was cost saving versus control [19]. Caro et al. evaluated the cost-effectiveness of lifestyle modification program in Canadian patients with abnormal glucose tolerance from the health payer perspective [20]. Cost per life year gained (LYG) was $749 in 2000 Canadian dollars. In a U.S. study by Herman et al. in 2005 [21], the lifestyle intervention versus placebo intervention was cost-effective with the ICER of about $1,100 per QALY gained.

However, a cost-effectiveness analysis using the DPP data in the U.S. from the societal perspective suggested the ICER of the lifestyle intervention versus standard care was approximately $62,600 per QALY gained which was not cost-effective using a WTP threshold of $50,000 per QALY gained [22]. The sensitivity analysis, however, demonstrated the lifestyle intervention for high-risk population could be cost saving if the annual cost of intervention can be reduced to about $100. This study came under heavy criticism, with doubt cast on its conclusions due to the perceived unrealistic assumptions used by the authors [19][23].

Despite one recent criticism of cost-effectiveness modelling studies of diabetes preventions [24], a within-trial economic evaluation by DPP/DPPOS group (not using modelling, rather using only data gathered purely from the clinical trial and follow-up study) confirmed that lifestyle intervention was cost-effective compared with placebo, even after only a 10-year period [25]. This result largely corresponded with the majority of earlier modelling studies projecting data from DPP to a longer time horizon [19][20][21].

Pharmacological interventions

RCTs have demonstrated several pharmacologic interventions can reduce the risk of type 2 diabetes, among which metformin was intensively studied in economic evaluations and was projected to be either cost-saving or highly cost-effective. It was cost-saving compared with no intervention in a Canadian context [20], as well as cost saving compared with intensive lifestyle changes in Australian, French, German and Swiss settings [17]; and cost saving compared to standard treatment in the U.S. health system and societal perspective [14].

Metformin was cost-effective in the U.K. setting with the ICER of $6,500 per LYG comparing with standard advice on lifestyle [17]. Similarly, metformin was shown to be cost-effective in the U.S. setting. The within-trial cost-effectiveness analysis from DPP in 2003 [15] determined metformin intervention was cost-effective with an ICER of $29,000 per QALY gained. Eddy et al. determined the ICER for intervention with metformin comparing with no intervention was $47,900 per QALY gained from the societal perspective [22]. Herman et al. determined the ICER for metformin versus placebo was $31,286 [21]. The ICER for metformin versus control in an Australian study by Palmer et al was $10,142 per QALY gained.

As well as metformin, acarbose was also found to be cost-effective in patients with IGT. Quilici et al determined the cost per patient free from type 2 diabetes was SEK 28,000 in a Swedish setting [26]. Acarbose was more costly than metformin but more effective and cost-effective, the cost per LYG was $1,798 CAD from the Canadian healthcare perspective [20].

Challenges in economic evaluation in T2DM preventions

The future economic evaluations in T2DM prevention need to address four main aspects:

  1. translational research from trial-based interventions to community-based program;
  2. generalizability of the results obtained from developed countries to developing countries;
  3. the role of bariatric surgery in the prevention of T2DM;
  4. diabetes prevention in lower risk populations

Clinical trials have shown some interventions were effective in reducing the development of T2DM in patients with IGT, but whether the results could be directly used in real-world interventions is of concern to both clinicians and health economists. Again, there will be a need to balance different effectiveness of diabetes prevention interventions in the community setting versus the addition costs of the intervention, both of which are likely to be lower in the real world, non-clinical trial environment. There are already several studies demonstrating the effectiveness of community-based interventions [27][28], and more evidence will be released from the on-going studies [29][30]. Future economic evaluations will be required to assess their cost-effectiveness in this setting.

Although 80% people with diabetes live in developing countries [31], limited evidence exists for the cost-effectiveness of diabetes prevention interventions in the developing world. Due to different costs of implementing diabetes prevention interventions, and vastly different costs of treating diabetes and its complications, it is not recommended to take the results of cost-effectiveness analyses from developed countries and assume that the same results will apply in the developing world. It was demonstrated from a within-trial analysis that both lifestyle and metformin interventions were cost-effective versus standard care in the Indian setting, [32], however a long term projection beyond the trial period is lacking. More studies are encouraged in developing countries, including clinical trials/community-based T2DM preventions programs, as well as supporting studies that quantify the costs and health state utility values of people with normal glycemic tolerance, abnormal glucose tolerance, as well as T2DM in country-specific settings in the developing world. Once these data have been obtained, economic evaluations of diabetes prevention can be performed with increased reliability in developing countries.

In addition to being a potentially effective treatment of diabetes in obese subjects [33], bariatric surgery has emerged as a potential major breakthrough in diabetes prevention in obese people, with the incidence of T2DM of 6.8 cases per 1000 person-years in bariatric surgery group versus 28.4 cases per 1000 person-years in control group over 15 years following bariatric surgery [34]. However, the cost-effectiveness of bariatric surgery for the prevention of T2DM has not been adequately assessed in most countries, although future analyses should be of high priority.

Finally, the majority of studies of diabetes prevention to date have been carried out in high risk populations; i.e. in subjects who are overweight or obese and with abnormal glucose tolerance. Broad-based diabetes prevention interventions, such as changes to the built environment and food taxation policies that have an impact on the general population will need to be explored both from the health outcome perspective as well as the health economic impact.

References

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